Haemophilus ducreyi is the causative agent of charoid, a sexually transmitted genital ulcerative disease. Chancroid is common in the developing world and occurs sporadically in North America. IN addition to the morbidity due to chancroid, genital ulcers are thought to facilitate the heterosexual transmission of HIV. The molecular mechanism(s) responsible for the formation of the chancroid ulcer are not known. The available data indicate that the lipoolgosaccaride (LOS) produced by H. ducreyi is an important virulence determinant. The principles investigator will characterize genes and gene products involved in the biosynthesis of H. ducreyi LOS and construct a series of isogenic strains that differ in the structure of their LOS. These strains will be tested in vitro models and in experimental human challenge studies in order to assess the role of the LOS in virulence and ulcer formation. These experiments will provide detailed information on the role of the LOS in pathogenesis, and structural requirements of the LOS which are critical for virulence. The data obtained in these studies will be pivotal to understanding the pathogenesis of chancroid and will provide insight into strategies for the prevention of this disease.